Ruxolitinib, Human Chorionic Gonadotropin (uhCG/EGF), and Dose De-escalated Corticosteroids

NCT ID: NCT05123040

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-05
• Study Completion Date: 2028-09-30

Brief Summary

This multi-center center phase I/II study to establish the lowest possible recommended phase 2 dose (RP2D) of corticosteroids in conjunction with ruxolitinib and uhCG/EGF (a novel combination) for high-risk aGVHD.

This is a single arm study designed to determine the lowest dose of corticosteroids required (toxicity endpoint) without impairing GVHD complete response or partial response (CR/PR) at day 28 when given in conjunction with uhCG/EGF and ruxolitinib.

After completion of the corticosteroid dose finding, the final dose will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of efficacy of this novel drug combination for high-risk aGVHD.

Conditions

Acute-graft-versus-host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ruxolitinib;hCG (Pregnyl®) ;Corticosteroids

• Ruxolitinib 10 mg by mouth twice daily (with dose adjustments as indicated) through day 56, followed by taper
• hCG (Pregnyl®) 2,000 units/m2 SQ every other day x 3 doses, followed by twice weekly x 14 doses (total 17 doses through day 56)
• Corticosteroids (Prednisone, or IV methylprednisolone equivalent)

• Dose level 1 (starting dose) = 1 mg/kg
• Dose level 2 = 0.5 mg/kg
• Dose level 3 = 0.25 mg/kg
• Dose level 4 = 0.1 mg/kg
• Dose level 5 = 0 mg/kg

Group Type: EXPERIMENTAL

Ruxolitinib 10 MG Oral Tablet

Intervention Type: DRUG

By mouth twice daily through day 56, then tapered

hCG

Intervention Type: DRUG

2,000 units/m2 SQ every other day x 3 doses, followed by twice weekly x 14 doses

Corticosteroids

Intervention Type: DRUG

Dose level 1 (starting dose) = 1 mg/kg

• Dose level 2 = 0.5 mg/kg
• Dose level 3 = 0.25 mg/kg
• Dose level 4 = 0.1 mg/kg
• Dose level 5 = 0 mg/kg

• If dose level 1 is determined to be below the Recommended Phase 2 Dose (RP2D), the dose will be escalated:
• Dose level -1 = 1.5 mg/kg
• Dose level -2 = 2 mg/kg

Interventions

Ruxolitinib 10 MG Oral Tablet

By mouth twice daily through day 56, then tapered

Intervention Type: DRUG

hCG

2,000 units/m2 SQ every other day x 3 doses, followed by twice weekly x 14 doses

Intervention Type: DRUG

Corticosteroids

Dose level 1 (starting dose) = 1 mg/kg

• Dose level 2 = 0.5 mg/kg
• Dose level 3 = 0.25 mg/kg
• Dose level 4 = 0.1 mg/kg
• Dose level 5 = 0 mg/kg

• If dose level 1 is determined to be below the Recommended Phase 2 Dose (RP2D), the dose will be escalated:
• Dose level -1 = 1.5 mg/kg
• Dose level -2 = 2 mg/kg

Intervention Type: DRUG

Other Intervention Names

Pregnyl; Prednisone; IV methylprednisolone

Eligibility Criteria

Inclusion Criteria

HCT recipients over 12 years of age within the first 7 days of initial treatment of high-risk aGVHD, defined as:

• Newly diagnosed Minnesota high-risk aGVHD -OR-
• Newly diagnosed Minnesota standard risk aGVHD with plasma amphiregulin ≥ 33 pg/ml tested at the UMN Cytokine Reference Lab. For amphiregulin lab ordering information, see Fairview Lab Guide: http://labguide.fairview.org/showtest.asp?testid=6766&format=long -OR-
• Newly diagnosed Minnesota standard risk aGVHD Ann Arbor 3 biomarkers tested by Viracor. For ordering information, see: https://www.viracor-eurofins.com/test-menu/403572p-agvhd-symptomatic- onset-algorithm/

• Renal: Serum creatinine ≤2.5x upper limit of normal (ULN)
• Cardiac: Left ventricular ejection fraction (LVEF) ≥ 35%
• Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17-year-olds).

Exclusion Criteria

• Progressive malignancy
• Uncontrolled bacterial, fungal, parasitic, or viral infection at initiation of protocol treatment
• Unwilling or unable to stop supplemental sex hormone therapy (estrogen, progesterone, and/or testosterone preparations)
• Unwilling or unable to stop GnRH antagonists, aromatase inhibitors, or anti-androgens
• History of a hormone responsive malignancy
• Current thromboembolic disease requiring full-dose anticoagulation - patients receiving pharmacologic prophylaxis for thromboembolic disease will be eligible
• Active or recent (within prior 3 months) thrombus, irrespective of anticoagulation status
• Pregnancy
• Women or men of childbearing potential unwilling to take adequate precautions to avoid unintended pregnancy from the start of protocol treatment through 30 days after the last treatment

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sherman Holtan, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Cancer Center Clinical Trials Office

Role: CONTACT

ccinfo@umn.edu

612 624 2620

Facility Contacts

Cancer Center Clinical Trials Office

Role: primary

ccinfo@umn.edu

612-624-2620

Other Identifiers

MT2020-28

Identifier Type: OTHER

Identifier Source: secondary_id

2020LS098

Identifier Type: -

Identifier Source: org_study_id